Myofibrillar Myopathies: New Perspectives from Animal Models to Potential Therapeutic Approaches

J Neuromuscul Dis. 2017;4(1):1-15. doi: 10.3233/JND-160203.

Abstract

Myofibrillar myopathies (MFMs) are muscular disorders involving proteins that play a role in the structure, maintenance processes and protein quality control mechanisms closely related to the Z-disc in the muscular fibers. MFMs share common histological characteristics including progressive disorganization of the interfibrillar network and protein aggregation. Currently no treatment is available. In this review, we describe first clinical symptoms associated with mutations of the six genes (DES, CRYAB, MYOT, ZASP, FLNC and BAG3) primary involved in MFM and defining the origin of this pathology. As mechanisms determining the aetiology of the disease remain unclear yet, several research teams have developed animal models from invertebrates to mammalians species. Thus we describe here these different models that often recapitulate human clinical symptoms. Therefore they are very useful for deeper studies to understand early molecular and progressive mechanisms determining the pathology. Finally in the last part, we emphasize on the potential therapeutic approaches for MFM that could be conducted in the future. In conclusion, this review offers a link from patients to future therapy through the use of MFMs animal models.

Keywords: MFM animal models; Myofibrillar myopathies; therapeutics.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Disease Models, Animal*
  • Drosophila*
  • Humans
  • Mice*
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / physiopathology
  • Mutation
  • Myopathies, Structural, Congenital / genetics
  • Myopathies, Structural, Congenital / pathology
  • Myopathies, Structural, Congenital / physiopathology*
  • Myopathies, Structural, Congenital / therapy
  • Oryzias*

Supplementary concepts

  • Myofibrillar Myopathy